Entity

Time filter

Source Type


Liu J.-Y.,China Medical University at Taichung | Lee M.-J.,Tian Sheng Memorial Hospital | Chen H.-M.,Fu Jen Catholic University | Tzang B.-S.,Chung Shan Medical University | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2011

Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the heart. O. gratissimum is one of the more well-known medicinal plants among the Ocimum species and widely used in treatment of inflammatory diseases. In this study, we hypothesized that aqueous extract of O. gratissimum leaf (OGE) may protect myocardiac cell H9c2 from oxidative injury by hydrogen peroxide (H2O2). Our results revealed that OGE pretreatment dose-dependently protects H9c2 cells from cell death when exposed to H2O2. Additionally, DNA condensation induced by H 2O2 was also reduced by OGE pretreatment, suggesting that Ocimum gratissimum extract may attenuate H2O2-induced chromosome damage. Further investigation showed that OGE pretreatment inhibited H2O2-induced activation of caspase-3 and caspase-9, as well as H2O2-induced upregulation of proapoptotic Apaf-1 and the release of cytosolic cytochrome c, but has little effect on the activation of caspase-8. Additionally, OGE pretreatment significantly upregulated Bcl-2 expression and Akt phosphorylation, and slightly affected the phosphorylation of mitogen-activated protein kinases including p38 MAPK and JNK. Taken together, our findings revealed that Ocimum gratissimum extract effectively inhibited the mitochondrial pathway and upregulated Bcl-2 expression, which may be important in protecting H9c2 cells from H 2O2-induced cell death. Source


Su C.-C.,Tian Sheng Memorial Hospital | Li S.-Y.,Chung Shan Medical University | Yen Y.-C.,Chi Mei Medical Center | Nian J.-H.,Chung Shan Medical University | And 2 more authors.
Cell Biochemistry and Biophysics | Year: 2013

Connexins (CXs), as a component of gap junction channel, are homologous four transmembrane-domain proteins, with numerous studies confirming their auditory functions. Among a cohort of patients having incurred non-syndromic hearing loss, we identified two novel missense mutations, p.R15G and p.L23H, in the GJC3 gene encoding CX30.2/CX31.3, as causally related to hearing loss in previous study. However, the functional alteration of CX30.2/CX31.3 caused by the mutant GJC3 gene remains unknown. In this study, we compared the intracellular distribution of mutant CX30.2/CX31.3 (p.R15G and p.L23H) with the wild-type (WT) protein in HeLa cells and the effect of the mutant protein had on those cells. Analytical results indicated that p.R15G and p.L23H mutant exhibited continuous staining along apposed cell membranes in the fluorescent localization assay, which is the same with the WT. Moreover, ATP release (hemichannel function) is less in HeLa cells carrying mutant GJC3 genes than those of WT expressing cells. We believe that although p.R15G and p.L23H mutants do not decrease the trafficking of CX proteins, mutations in GJC3 genes result in a loss of hemichannel function of CX30.2/CX31.3 protein, possibly causing hearing loss. Results of this study provide a novel molecular explanation for the role of GJC3 in hearing loss. © 2012 Springer Science+Business Media New York. Source


Li C.-S.,Tian Sheng Memorial Hospital | Schminke U.,University of Greifswald | Tan T.-Y.,Chang Gung University
Clinical Neurology and Neurosurgery | Year: 2010

Objective: Irradiation induced extracranial carotid occlusive disease has been recognized as a potential cause of post-irradiation stroke in nasopharyngeal carcinoma (NPC) patients. Our study aims to investigate the prevalence of extracranial CA disease in post-irradiated Taiwanese NPC ischemic stroke patients. Methods: Forty-threeNPCpatients with ischemic stroke were retrospectively selected from the stroke registration of the study hospital and compared with 276 first-ever ischemic stroke patients from the same database, of which 31 patients underwent carotid duplex sonography (CDS). Significant atherosclerotic lesions of the carotid arteries were defined as a >50% stenosis or an occlusion according to CDS. Results: Significant carotid lesions occurred in 13 of 31 (42%) NPC patients. Stroke was more frequently caused by large artery disease (44% versus 23%; p < 0.01) in NPC patients than in first-ever stroke patients without NPC. Carotid artery disease (odds ratio 7.22, 95% confidence interval 2.51-20.77; p < 0.0001) and absence of diabetes mellitus (odds ratio 0.26, 95% confidence interval 0.07-0.93; p = 0.039) were the strongest independent discriminators between NPC stroke patients and non-NPC stroke patients in a multivariate logistic regression analysis. Conclusion: Patients who received neck irradiation are at risk for the delayed development of diffused atherosclerosis but also for carotid occlusion within years, although the mechanism remains elusive and probably multifactorial. © 2010 Elsevier B.V. All rights reserved. Source


Hong H.-M.,Chung Shan Medical University | Yang J.-J.,Chung Shan Medical University | Su C.-C.,Tian Sheng Memorial Hospital | Chang J.-Y.,Chung Shan Medical University | And 2 more authors.
Human Genetics | Year: 2010

Connexins (Cxs) are homologous four-transmembrane domain proteins and constitute the major components of gap junctions. Among a cohort of patients with nonsyndromic hearing loss, we recently identified a novel missense mutation, E269D, in the GJC3 gene encoding connexin 29 (Cx29), as being causally related to hearing loss. The functional alteration of Cx29 caused by the mutant GJC3 gene, however, remains unknown. This study compared the intracellular distribution and assembly of mutant Cx29 (Cx29E269D) with that of the wild-type Cx29 (Cx29WT) in HeLa cells and the effect the mutant protein had on those cells. Cx29TW showed continuous staining along apposed cell membranes in the fluorescent localization assay. In contrast, the p.E269D missense mutation resulted in accumulation of the Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the cytoplasmic membrane. Co-expression of Cx29WT and Cx29E269D proteins by a bi-directional tet-on expression system demonstrated that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the formation of the gap junction. Based on these findings, we suggest that Cx29E269D has a dominant negative effect on the formation and function of the gap junction. These results provide a novel molecular explanation for the role Cx29 plays in the development of hearing loss. © 2009 Springer-Verlag. Source


Su C.-C.,Tian Sheng Memorial Hospital | Li S.-Y.,Chung Shan Medical University | Su M.-C.,Chung Shan Medical University | Chen W.-C.,Chung Shan Medical University | Yang J.-J.,Chung Shan Medical University
European Journal of Human Genetics | Year: 2010

Hearing impairment is the most common sensory disorder worldwide. In a recent study, the authors have shown that a heterozygous missense mutation, p.R184Q, in the connexin 26 (Cx26) is causally related to hearing loss. However, the functional change in the Cx26R184Q mutant remains unknown. This study compared the intracellular distribution and assembly of mutant Cx26R184Q with that of the wild-type (WT) Cx26 and Cx30WT in tet-on HeLa cells and the effect that the mutant protein had on those cells. Fluorescent localization assay of WT Cx26 showed the typical punctuate pattern of gap junction channel between neighboring expression cells. Conversely, the p.R184Q missense mutation resulted in accumulation of the Cx26 mutant protein in the Golgi apparatus rather than in the cytoplasmic membrane. Cx26R184Q coexpressed with either Cx26WT or Cx30WT showed perinuclear localization by bidirectional tet-on expression system, suggesting the impairment of the ability of both WT proteins to intracellular trafficking and targeting to the plasma membrane. Therefore, we proposed that Cx26R184Q has a dominant-negative effect on the function of WT Cx26 and Cx30. © 2010 Macmillan Publishers Limited All rights reserved. Source

Discover hidden collaborations